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Biomedical subjects

M A Farrell

Publications and source records attributed to M A Farrell.

At least 55 records · Page 3Linked to original sources

Chronic encephalitis associated with epilepsy: immunohistochemical and ultrastructural studies.

Chronic encephalitis has been recognized as a cause of epilepsy since the work of Rasmussen et al. in the late 1950s. Despite this, few immunohistochemical studies of the affected brain tissue have been attempted. We have studied specimens of brain tissue from seven patients with this condition who underwent therapeutic multilobar cortical resection or hemispherectomy. Immunohistochemical studies were carried out using antibodies to glial fibrillary acidic protein (GFAP), proliferating cell nuclear antigen (PCNA, PC10), T lymphocytes (UCHL-1), B lymphocytes (L26), macrophages and microglia (HAM-56), and major histocompatibility complex molecules (LN3 and beta 2-microglobulin). Additionally, the results of preliminary immunohistochemical and ultrastructural investigation of possible immune complex deposition in blood vessel walls of affected brain tissue are presented. The pattern of GFAP immunoreactivity suggested a patchy and/or laminar disease process in most patients. GFAP immunoreactive cells were especially prominent around microvessels in some cases, suggesting an abnormality and perivascular collections of inflammatory cells, seen to a variable extent in all cases, contained abundant cells immunolabelled with UCHL-1, LN3 and beta 2-microglobulin. L26-labelled B lymphocytes were extremely sparse. Anti-PCNA frequently labelled microvascular endothelial cells, rare pericytes and occasional cells with microglial/macrophage morphology. The data suggest that chronic encephalitis found in patients with epilepsy results from patchy but widespread parenchymal brain injury, in the course of which cells of both microglial and lymphocyte series accumulate or proliferate within brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Posterior thecal lumbar disc herniation mimicking synovial cyst.

We describe a 70 year-old-patient with a rare, misleading presentation of lumbar disc prolapse, which on CT mimicked a synovial cyst. The whole nucleus pulposus had herniated, become sequestrated, and migrated behind the theca adjacent to the L4-5 facet joint. There was no continuity of the disc material with the intervertebral space. A fenestration was performed and the sequestrated disc material was found free of adhesions, and removed completely without difficulty. Histopathological examination confirmed the diagnosis. The patient had complete relief from his pain.

Aged↗

Initial 'schizophrenia-like' psychosis in Pick's disease: case study with neuroimaging and neuropathology, and implications for frontotemporal dysfunction in schizophrenia.

'Schizophrenia-like' psychosis has not been reported previously as a prodrome of Pick's disease, a dementia of frontotemporal pathology. A woman having a consistent clinical diagnosis of typical schizophrenia who developed increasing affectivity and cognitive deficits was examined by computed tomography and brain biopsy. This presentation was found to be associated with left frontotemporal atrophy, left sylvian fissure abnormalities and enlargement of the anterior and temporal horns of the left lateral ventricle. On biopsy, all the neuropathological hallmarks of Pick's disease were present. Unusually, some specific aspect of Pick's disease in this patient appears initially to have disturbed brain function in a manner reproducing some fundamental aspect(s) of schizophrenia itself; left frontotemporal dysfunction would appear to be a relevant common denominator.

Aged↗

Intracranial metastases from pituitary adenoma.

Two patients with histologically benign pituitary adenomas subsequently underwent resections of a frontal and a cerebellar tumour each of which had histological appearances identical to those of classic pituitary adenomas. The frontal tumour was immunoreactive for prolactin, and the cerebellar metastasis was immunoreactive for thyrotropin and gonadotrophins. There was no evidence of residual or recurrent intrasellar pituitary adenoma, nor was there a connection between the frontal or cerebellar masses and the sella turcica. Extracranial tumours have not developed. Both tumours fulfil criteria for diagnosis of pituitary carcinoma. These rare tumours are reviewed with emphasis on diagnosis and management.

Adenoma↗

Neuropathic findings in oculopharyngeal muscular dystrophy. A report of seven cases and a review of the literature.

We describe seven patients with clinical evidence of oculopharyngeal muscular dystrophy. Four of these patients were members of the same Italian-American family. The age at onset was after the fourth decade in all patients. All seven patients had extraocular muscle involvement, and six of the seven patients had clinical, electrophysiological, and/or pathological evidence of neuropathy in addition to features that were suggestive of myopathy. An autopsy was performed on one patient. We discuss the significance of the concurrence of neuropathic features with oculopharyngeal muscular dystrophy in relation to these patients and previously reported cases.

Aged↗

Prevalence of diabetes and its complications in the Eastern Band of Cherokee Indians.

OBJECTIVE: To determine the prevalence of diabetes and selected complications among the Eastern Band of Cherokee Indians in North Carolina. RESEARCH DESIGN AND METHODS: Multiple IHS data systems were used to determine diabetes prevalence and complication rates. The RPMS was used to identify diabetes cases as of April 1989, degree of Indian inheritance, cardiovascular diseases (including hypertension), and retinopathy. Data on laser treatments and LEA were obtained from individual registries. Information on ESRD was obtained by a research assistant. The IHS Ambulatory Patient Care reporting system was used to calculate the number of diabetic patients for the years 1982-1987. The IHS user population was used as the denominator. Rates were age-adjusted to the 1980 U.S. population and diabetic population by the direct method. RESULTS: Using clinical records, the age-adjusted prevalence of diabetes in 1988 was 105.6/1000 people, four times the U.S. rate. Rates of diabetes were highest in the groups with the highest degree of Indian inheritance. LEAs occurred among diabetic patients at three times the rate for the U.S. Between 1985 and 1989, new cases of ESRD occurred at a crude annualized rate of 578/million, approximately six times the rate for U.S. whites. CONCLUSIONS: Diabetes presents a major burden to the Eastern Band of Cherokees. The limitation inherent in this study probably result in underestimation of the prevalence of diabetes and its complications in the community. Future studies are needed to assess the impact of medical and preventive programs on diabetes prevalence and complications in this community.

Adult↗

Renal disease among the Eastern Band of Cherokee Indians.

OBJECTIVE: To ascertain the incidence and prevalence of ESRD in the Eastern Band of Cherokee in the IHS user population from 1978 to 1988 and to determine what proportion of ESRD and chronic renal failure is attributable to diabetes. RESEARCH DESIGN AND METHODS: Cases were identified from three IHS data sources and from death records obtained from the North Carolina Bureau of Health Statistics. Chronic renal insufficiency was defined as an individual having a serum creatinine of > or = 176.8 microM that remained at that level for a sustained period. An ESRD case was defined as one in which dialysis was required to sustain life, regardless of whether treatment was actually implemented. Data were obtained from chart review and included date of diagnosis, maximum serum creatine level attained, diabetes status, and certain demographic data. RESULTS: Twenty-two (88%) cases of ESRD were attributable to diabetes. The average annual incidence of ESRD during the study period was much higher than that in the U.S. white population and that of Native Americans. The incidence of ESRD caused by diabetes was 2.5 times higher than that reported in the U.S. Native American population affected by diabetes. Degree of Indian inheritance did not appear to be related to prevalence of diabetic renal disease in individuals having diagnosed diabetes. CONCLUSIONS: The proportion of ESRD attributable to diabetes indicates that primary prevention of diabetes may be the best method of preventing ESRD in this population.

Cause of Death↗

Neuropathologic findings in cortical resections (including hemispherectomies) performed for the treatment of intractable childhood epilepsy.

Despite the use of hemispherectomy in the treatment of medically refractory seizures since the early 1950's, few studies published have documented neuropathologic findings in the resected specimens. This report describes the neuropathologic findings in 38 children who underwent either hemispherectomy or multilobar cortical resection as treatment for medically intractable epilepsy between 1986 and 1990. Examination of the resected specimens revealed a variety of abnormalities which fell into four broad categories. Malformations or hamartomatous lesions were the dominant finding in 15 patients, whereas encephalomalacic lesions were the most prominent abnormality in 16; chronic pathogen-free encephalitits (Rasmussen's encephalitis) was present in 3 and an additional 3 children had Sturge-Weber-Dimitri syndrome. There were no gross or microscopic abnormalities in 1 patient. This report provides the first comprehensive description of the pathologic findings in a series of children with refractory epilepsy of varying types treated by hemispherectomy-multilobar resection.

Brain Ischemia↗

Spinal cord infarction caused by cartilage embolus to the anterior spinal artery.

Cartilaginous embolization of spinal vessels is a rare cause of spinal cord infarction. A 63-year-old woman developed sudden onset of painful, fatal paraparesis following a valsalva-like maneuver. Autopsy demonstrated recent nonhemorrhagic infarction of the caudal thoracic spinal cord secondary to complete occlusion of the anterior spinal artery by cartilage. The literature pertaining to 28 previously reported cases is briefly reviewed.

Cartilage↗

An assessment of the proliferative potential of 'balloon cells' in focal cortical resections performed for childhood epilepsy.

Cerebral cortical dysplasia is an uncommon pathological substrate of severe intractable childhood epilepsy, sometimes treated by hemispherectomy. Neuropathological findings include abnormal gyrus formation, loss of cortical lamination, unusual giant neurons and 'balloon cells' of indeterminate histogenesis similar in appearance to neoplastic gemistocytic astrocytes. In order to investigate the proliferative potential of 'balloon cells', we used Crocker's silver impregnation technique to demonstrate nucleolar organizer regions (AgNORs) involved in cellular proliferation, together with immunohistochemical evaluation of proliferating cell nuclear antigen (PCNA) expression. Balloon cells (5.56 +/- 0.24) had significantly (P < 0.001) greater AgNOR numbers than reactive astrocytes (3.89 +/- 0.15), neurons (2.30 +/- 0.13) or giant neurons (4.26 +/- 0.20). However, when corrected for nuclear size, results showed that 'balloon cells' (0.093 +/- 0.006) had significantly (P < 0.001) fewer AgNORs/square micrometre of nuclear area than reactive astrocytes (0.225 +/- 0.016) and had significantly (P < 0.001) more AgNORs/square micrometre of nuclear area than normal (0.048 +/- 0.003) or giant neurons (0.054 +/- 0.003). On the assumption that astrocytes are typical interphase cells and that normal neurons are post-mitotic, the results suggest that 'balloon cells' are unlikely to be undergoing proliferative activity and, when adjusted for nuclear size, the number of AgNORs/unit of nuclear area is more reflective of cellular ploidy than of proliferative activity in non-neoplastic neural tissues. The virtual absence of PCNA expression by 'balloon cell' nuclei supports such an interpretation of the AgNOR results.

Cell Count↗

Neuropathologic findings in AIDS and human immunodeficiency virus infection--report on 30 patients.

Central nervous system findings in 30 fatal cases of human immune deficiency viral (HIV) infection are described. Twenty seven patients had acquired immune deficiency syndrome (AIDS) and three patients had serological evidence of HIV infection only (HIV seropositive). Twenty nine patients had neuropathologic abnormalities at autopsy and frequently had more than one neuropathologic process. Neurologic disease was the dominant clinical feature in nineteen patients. The spectrum of neuropathologic disease is similar to that described in other series encompassing direct HIV infection of brain; indirect CNS involvement by opportunistic pathogens differing slightly from other series in their relative frequency; lymphoma and neurovascular disease. This, the first report which serves to document the level of neurologic disease in Irish patients with AIDS and HIV infection should help to provide meaningful information for use in the planning of neurologic and rehabilitation services for these patients.

Acquired Immunodeficiency Syndrome↗

Effect of ions on binding of the thiazide-type diuretic metolazone to kidney membrane.

The effect of a number of ions on the binding of the thiazide-type diuretic metolazone (MTZ) to rat renal cortical membranes was studied to elucidate the mechanism of NaCl transport in the kidney distal tubule. Among the cations tested, Na+ significantly stimulated the binding up to 2.4-fold over control. The effective concentration of Na+ that produced half-maximal stimulation was 2-17 mM. Li+, K+, NH4+, Rb+, and Cs+ produced little stimulation of binding of MTZ. Several anions including Cl- inhibited binding. The inhibition of binding of MTZ by Cl- was enhanced by Na+ and Li+. Scatchard analyses revealed that 50 mM Na+ increased the affinity for binding of MTZ from a Kd = 3.56 +/- 0.15 nM to Kd = 1.32 +/- 0.11 nM. Chloride, in the presence of 50 mM Na+, competitively inhibited binding of MTZ by suppressing the affinity to Kd = 9.27 +/- 1.11 nM without changing the maximal number of binding sites (0.733 +/- 0.049 pmol/mg). A mechanism for the MTZ-sensitive NaCl transport is proposed, in which the transporter protein possesses a binding site for Na+ and a binding site for Cl-, which is also the binding site for MTZ. Na+ binds to its site and increases the affinity for Cl-/MTZ. The binding of Cl- to the transporter enables the import of Na+ and Cl- across the tubule membrane. MTZ, however, when present competes with Cl- for the binding site on the transporter and prevents the transport of Na+ and Cl-.

Animals↗

Microdysgenesis in resected temporal neocortex: incidence and clinical significance in focal epilepsy.

Fifty patients underwent superficial temporal lobectomy for intractable temporal lobe epilepsy. Total cure rate was 52%, and significant improvement was achieved in 88%. Cytoarchitectural changes in gray and white tissue were analyzed under light microscopy. Neuronal dysgenesis was correlated with the duration of seizure disorder, age of onset, and other etiologic factors, and with clinical outcome. Temporal lobes from 33 neurologically normal autopsy brains which were age- and sex-matched with patients were examined as controls. Severe neuronal ectopia (greater than 8 neurons/2 mm2 white matter) was present in 42% of patients with epilepsy and in none of controls. There was neuronal clustering in 28% of those with epilepsy, and Chaslin's (subpial) gliosis in 38%. Controls did not have these changes. The presence of severe neuronal ectopia and clustering was predictive of a favorable clinical outcome following surgery (p less than 0.05). No correlation was found between microdysgenesis and other factors. These findings suggest that the presence of neuronal dysgenesis may be of significance in the clinical outcome following surgery, and that the abnormal tissue may be important as a morphologic substrate for seizures in some patients.

Adolescent↗